Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease.,Cell

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Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease.
Cell ( IF 45.5 ) Pub Date : 2017-Oct-05 , DOI: 10.1016/j.cell.2017.09.021
Brent R Stockwell ₁ , José Pedro Friedmann Angeli ₂ , Hülya Bayir ₃ , Ashley I Bush ₄ , Marcus Conrad ₂ , Scott J Dixon ₅ , Simone Fulda ₆ , Sergio Gascón ₇ , Stavroula K Hatzios ₈ , Valerian E Kagan ₉ , Kay Noel ₁₀ , Xuejun Jiang ₁₁ , Andreas Linkermann ₁₂ , Maureen E Murphy ₁₃ , Michael Overholtzer ₁₁ , Atsushi Oyagi ₁₄ , Gabriela C Pagnussat ₁₅ , Jason Park ₁₆ , Qitao Ran ₁₇ , Craig S Rosenfeld ₁₀ , Konstantin Salnikow ₁₈ , Daolin Tang ₁₉ , Frank M Torti ₂₀ , Suzy V Torti ₂₁ , Shinya Toyokuni ₂₂ , K A Woerpel ₂₃ , Donna D Zhang ₂₄

Affiliation

Department of Biological Sciences, Columbia University, 550 West 120(th) Street, MC 4846, New York, NY 10027, USA; Department of Chemistry, Columbia University, 550 West 120(th) Street, MC 4846, New York, NY 10027, USA.
Institute of Developmental Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), München, Germany.
Department of Critical Care Medicine, Safar Center for Resuscitation Research and Center for Free Radical and Antioxidant Health, University of Pittsburgh and Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
Department of Biology, Stanford University, Stanford, CA, USA.
Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, German Cancer Consortium (DKTK), partner site Frankfurt, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Ludwig-Maximilians University of Munich, Physiological Genomics, Biomedical Center (BMC), Planegg-Martinsried, Germany; Institute for Stem Cell Research, Helmholtz Center Munich at the Biomedical Center (BMC), Grosshaderner Strasse 9, 82152 Planegg-Martinsried, Germany.
Department of Molecular, Cellular and Developmental Biology and Department of Chemistry, Yale University, New Haven, CT 06511, USA; Microbial Sciences Institute, Yale University, West Haven, CT 06516, USA.
Center for Free Radical and Antioxidant Health, Departments of Environmental Health, Pharmacology and Chemical Biology, Chemistry, Radiation Oncology, University of Pittsburgh, Pittsburgh, PA, USA.
Collaborative Medicinal Development, LLC, Sausalito, CA, USA.
Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Internal Medicine III, Division of Nephrology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
Program in Molecular and Cellular Oncogenesis, The Wistar Institute, Philadelphia, PA, USA.
Ono Pharma USA, Lawrenceville, NJ 08648, USA.
Instituto de Investigaciones Biológicas, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Mar del Plata, 7600 Mar del Plata, Argentina.
Flagship Pioneering, Cambridge, MA, USA.
Department of Cell Systems and Anatomy, University of Texas Health Science Center, San Antonio, TX, USA.
Division of Cancer Biology, National Cancer Institute, NIH, Rockville, MD 20850, USA.
The Third Affiliated Hospital, Center for DAMP Biology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Protein Modification and Degradation Laboratory, Guangzhou Medical University, Guangzhou, Guangdong, China; Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA.
Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT, USA.
Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Chemistry, New York University, New York, NY, USA.
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, USA.

Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q₁₀. Ferroptosis has been implicated in the pathological cell death associated with degenerative diseases (i.e., Alzheimer's, Huntington's, and Parkinson's diseases), carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration in mammals and is also implicated in heat stress in plants. Ferroptosis may also have a tumor-suppressor function that could be harnessed for cancer therapy. This Primer reviews the mechanisms underlying ferroptosis, highlights connections to other areas of biology and medicine, and recommends tools and guidelines for studying this emerging form of regulated cell death.

中文翻译：

铁死亡：连接代谢、氧化还原生物学和疾病的受调节细胞死亡关系。

铁死亡是一种受调节的细胞死亡形式，其特征是铁依赖性脂质过氧化氢累积至致死水平。新出现的证据表明，铁死亡代表了一种古老的脆弱性，是由多不饱和脂肪酸掺入细胞膜引起的，并且细胞已经开发出复杂的系统，可以在不同的情况下利用和防御这种脆弱性。对铁死亡的敏感性与许多生物过程密切相关，包括氨基酸、铁和多不饱和脂肪酸代谢，以及谷胱甘肽、磷脂、NADPH 和辅酶 Q ₁₀的生物合成。铁死亡与哺乳动物退行性疾病（即阿尔茨海默病、亨廷顿病和帕金森病）、癌发生、中风、脑出血、创伤性脑损伤、缺血再灌注损伤和肾变性相关的病理性细胞死亡有关，并且还与在植物的热应激中。铁死亡还可能具有肿瘤抑制功能，可用于癌症治疗。本入门书回顾了铁死亡的机制，强调了与生物学和医学其他领域的联系，并推荐了研究这种新兴形式的受调节细胞死亡的工具和指南。

更新日期：2017-10-05

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